Bacterial symbioses are ubiquitous in nature, yet to date few studies have been performed to determine the physiological mechanisms that underlie these relationships. Insects represent a group of advanced multi-cellular organisms that harbor well- documented symbiotic associations. One such insect, the tsetse fly (Glossina spp.), harbors 2 maternally-transmitted bacterial symbionts, mutualistic Wigglesworthia and commensal Sodalis, that are intimately involved in maintaining the overall fitness of their host. Specifically, when immature tsetse flies develop in the absence of their endogenous microbiota, subsequent 'aposymbiotic' adults are highly susceptible to infection with normally non-pathogenic E. coli. This susceptible phenotype is characterized by highly compromised cellular and humoral immunity. In this study we will next generation sequencing technologies to investigate the molecular mechanisms that underlie symbiont-induced immune system maturation in tsetse. This fly serves as the sole vector pathogenic African trypanosomes, which cause sleeping sickness in humans and Nagana in domesticated animals. Knowledge gained by completing this work can be used to reduce disease transmission through tsetse, as well as other insects (such as mosquitoes) that house symbiotic bacteria and vector human pathogens. Furthermore, basic concepts related to the genetics that underlie symbiont-induced immunity in tsetse may be of fundamental importance to mammalian immunology. PUBLIC HEALTH RELEVANCE: Tsetse flies harbor symbiotic bacteria that induce the development of their host's immune system. We will use this model system to acquire a better understanding of the molecular mechanisms that underlie symbiont-mediate development of animal immunity. This information will be applicable to controlling a wide range of human pathologies, ranging from Human African trypanosomiasis to Crohn's disease.